The purpose of this proposal is to investigate the effects of alcohol exposure on cerebral blood flow during the third trimester in sheep. Neurological deficits are the most devastating consequences of maternal alcohol abuse. In spite of the huge research literature on this subject, surprisingly little is known about the mechanisms underlying alcohol's effects. One possible mechanism may be associated with fetal cerebral blood flow, since the neurovasculature is so important for proper neurodevelopment. The data generated from this proposal will help to further our understanding of the mechanisms of fetal alcohol-induced brain damage. The goals will be addressed in two specific aims using a sheep model system. SPECIFIC AIM #1 will test the hypothesis that repeated alcohol exposure will adversely affect fetal cerebral blood flow. SPECIFIC AIM #2 will test the hypothesis that repeated alcohol exposure will affect the neurovascular responsiveness to acute alcohol exposure. These experiments will be performed using the sheep model system in order to maintain an intact maternal/fetal unit. Regional blood flow will be measured in fetal sheep in utero using radiotabelled microspheres. Understanding alcohol's effects during development will be helpful in the future for guiding prevention and therapy strategies.